Fair evaluation of federated learning algorithms for automated breast density classification: The results of the 2022 ACR-NCI-NVIDIA federated learning challenge.

The correct interpretation of breast density is important in the assessment of breast cancer risk. AI has been shown capable of accurately predicting breast density, however, due to the differences in imaging characteristics across mammography systems, models built using data from one system do not generalize well to other systems. Though federated learning (FL) has emerged as a way to improve the generalizability of AI without the need to share data, the best way to preserve features from all training data during FL is an active area of research. To explore FL methodology, the breast density classification FL challenge was hosted in partnership with the American College of Radiology, Harvard Medical Schools' Mass General Brigham, University of Colorado, NVIDIA, and the National Institutes of Health National Cancer Institute. Challenge participants were able to submit docker containers capable of implementing FL on three simulated medical facilities, each containing a unique large mammography dataset. The breast density FL challenge ran from June 15 to September 5, 2022, attracting seven finalists from around the world. The winning FL submission reached a linear kappa score of 0.653 on the challenge test data and 0.413 on an external testing dataset, scoring comparably to a model trained on the same data in a central location.

Covid-19 vaccination coverage and associated factors among older hypertensive patients in Hangzhou, China.

BACKGROUND: Vaccination could provide effective protection against coronavirus disease 2019 (COVID-19). This study aims to describe the COVID-19 vaccination coverage and influential factors in Chinese older hypertensive patients. METHODS: Using a cross-sectional design, participants were randomly selected from the electronic health records system during the pandemic era in Hangzhou, China. Logistic regression models were employed to compute the OR and 95% CI in order to assess the relationships between variables and the extent of COVID-19 vaccination coverage. RESULTS: As of 3 August 2022, among a sample of 77 970 individuals, 75.11% had completed the full COVID-19 vaccination, while 57.66% had received a booster dose. Disparities in coverage were observed across genders, regions and age groups. Unhealthy lifestyles, cardiovascular disease, cancer, uncontrolled blood pressure, abnormal fasting plasma glucose, dyslipidemia and renal dysfunction were risk factors for COVID-19 vaccination coverage. The coverage rates continuously declined along with the number of risk factors. The ORs for full and booster vaccination in subjects with ≥4 risk factors were 2.55 (2.12∼3.07) and 2.60 (2.16∼3.13), compared to individuals without risk factors. CONCLUSION: The COVID-19 vaccination program for older hypertensive patients must be strengthened further. Emphasis should be placed on patients who reside in urban areas, have comorbidities or multiple risk factors.

Construction of a Prognostic Model Based on Methylation-Related Genes in Patients with Colon Adenocarcinoma.

Purpose: Colon adenocarcinoma (COAD) is the second leading cause of death in the world, and the new incidence rate ranks third among all cancers. Abnormal DNA methylation is related to the occurrence and development of tumors. In this study, we aimed to identify genes associated with abnormal methylation in COAD. Methods: COAD transcriptome data, methylation data and clinical information were downloaded from the TCGA database and GEO database. The differentially expressed genes (DEGs) and methylated genes (DMGs) were analyzed and identified in COAD. PCA analysis was applied to divide COAD into subtypes, and the survival and immune cell infiltration of each subtype were evaluated. Cox and LASSO analyses were performed to construct COAD risk model. GSEA was used to evaluate the enrichment pathways. The Kaplan-Meier was used to analyze the difference in survival. ROC curve was plotted to evaluate the accuracy of the model, and GSE17536 was used to verify the accuracy of the risk model. The risk model is combined with the clinicopathological characteristics of COAD patients to perform multivariate Cox regression analysis to obtain independent risk factors and draw nomograms. Results: In total, 4564 DEGs and 1093 DMGs were screened, among which 298 were found to be overlapping genes. For 220 of these overlapping genes, the methylation was significantly negatively correlated to expression levels. An optimal signature from 4 methylated biomarkers was identified to construct the prognostic model. Conclusion: Our study identified 4 methylated biomarkers in the COAD. Then, we constructed the risk model to provide a theoretical basis and reference value for the research and treatment of COAD.

Application of Inflatable Video-Assisted Mediastinoscopic Transhiatal Esophagectomy in Individualized Treatment of Esophageal Cancer.

Surgery is a crucial treatment option for patients with resectable esophageal cancer. The emergence of minimally invasive esophageal techniques has led to the popularity of video-assisted thoracoscopic esophagectomy, which has proven to be more advantageous than traditional thoracotomy. However, some patients with esophageal cancer may not benefit from this procedure. Individualized treatment plans may be necessary for patients with varying conditions and tolerances to anesthesia, making conventional surgical methods unsuitable. Inflatable video-assisted mediastinoscopic transhiatal esophagectomy (IVMTE) has emerged as a promising treatment option for esophageal cancer because it does not require one-lung ventilation, reduces postoperative complications, and expands surgical indications. This technique also provides surgical opportunities for patients with impaired pulmonary function or thoracic lesions. It is crucial to have a comprehensive understanding of the advancements and limitations of IVMTE to tailor treatment plans and improve outcomes in patients with esophageal cancer. Understanding the advantages and limitations of this surgical method will help specific patients with esophageal cancer. We conducted a thorough review of the relevant literature to examine the importance of IVMTE for individualized treatment of this disease.

Rapid and accurate genotyping of human SNP rs671 in aldehyde dehydrogenase 2 gene using one-step CRISPR/Cas12b assay without DNA amplification.

BACKGROUND: The SNP rs671 of Human aldehyde dehydrogenase (ALDH) is G-A transition at 1510th nucleotides, which is an important clinical indicator of alcoholic liver disease, digestive tract cancer and some drug efficiency. The commonly used genotyping assay of this polymorphism is relatively time-consuming and costly. FINDING: This study develops a rapid and accurate one-step CRISPR/Cas12b assay to distinguish the G1510A polymorphism of human ALDH2 free of DNA amplification. The method we established requires only one step of adding 1 µl genomic DNA sample to premixed system, and waiting for the acquisition of fluorescent signal, taking approximate 30 min. CONCLUSIONS: This method provides a potential tool for more accurate and reliable nucleic acid detection with a single base difference and supports the relevant disease diagnosis and personalized medicine.

Real-world vaccination status of children with hematologic tumors before and after chemotherapy.

BACKGROUND: There is a high incidence and mortality rate in children with hematologic tumors (CHT), who are more prone to various infectious diseases. This study aims to clarify the real-world National Immunization Program (NIP) vaccination status of CHT before and after chemotherapy. METHODS: Medical records, NIP vaccination data, and the Adverse Event Following Immunization (AEFI) of CHT who were admitted to the Children's Hospital, Zhejiang University School of Medicine, from 1 January 2011 to 1 December 2021 were completely collected. RESULTS: A total of 2,874 CHT were included, and 1975 (68.7%) had vaccination records. Among the enrolled patients, the vaccination rate of all NIP vaccines was lower than 90% before diagnosis. Only 24.29% of CHT (410/1688) resumed vaccination after chemotherapy, and 69.02% (283/410) resumed vaccination more than 12 months after chemotherapy. No uncommon or serious side effects were reported. CONCLUSION: The vaccination rate of CHT after chemotherapy was lower than that before the disease was diagnosed. It is necessary to provide more evidence-based support and formulate specific regimens to perfect the vaccination procedure after chemotherapy so as to improve the quality of life of CHT.

Current vaccination status and safety of children with peripheral neuroblastoma in the real-world.

Background: peripheral neuroblastic tumors (pNT) have high incidence and mortality, and infants are prone to various infectious diseases. The purpose of this study is to understand the immunization status of children with pNT in the real-world and the incidence of adverse reactions after vaccination, and to evaluate the feasibility of vaccination and the influencing factors of vaccination. Methods: Children with pNT treated in the Children's Hospital Affiliated to Zhejiang University from January 1, 2011 to December 1, 2021 were included. By referring to medical records, the vaccination history of the national immunization program (NIP) vaccines and the occurrence of adverse events following immunization(AEFI), current status and safety of immunization in children with pNT in the real-world were analyzed. Results: Among 784 children with pNT, 394 were able to obtain the history of vaccination. The overall vaccination rate of NIP vaccines was 71.49% before chemotherapy and 37.67% after chemotherapy, and the recovery time of vaccination after treatment was 16.00 (6.00,24.00) months. Age, time of tumor diagnosis and disease classification were significantly correlated with vaccination. AEFI reported an incidence of 0.23‰. Conclusion: The vaccination rate of children with pNT is generally low, especially the vaccination rate after chemotherapy. The vaccination safety is good, children should be encouraged to immunize.

Targeting cancer-related inflammation with non-steroidal anti-inflammatory drugs: Perspectives in pharmacogenomics.

Inflammatory processes are essential for innate immunity and contribute to carcinogenesis in various malignancies, such as colorectal cancer, esophageal cancer and lung cancer. Pharmacotherapies targeting inflammation have the potential to reduce the risk of carcinogenesis and improve therapeutic efficacy of existing anti-cancer treatment. Non-steroidal anti-inflammatory drugs (NSAIDs), comprising a variety of structurally different chemicals that can inhibit cyclooxygenase (COX) enzymes and other COX-independent pathways, are originally used to treat inflammatory diseases, but their preventive and therapeutic potential for cancers have also attracted researchers' attention. Pharmacogenomic variability, including distinct genetic characteristics among different patients, can significantly affect pharmacokinetics and effectiveness of NSAIDs, which might determine the preventive or therapeutic success for cancer patients. Hence, a more comprehensive understanding in pharmacogenomic characteristics of NSAIDs and cancer-related inflammation would provide new insights into this appealing strategy. In this review, the up-to-date advances in clinical and experimental researches targeting cancer-related inflammation with NSAIDs are presented, and the potential of pharmacogenomics are discussed as well.

Interfering HMGB3 release from cancer-associated fibroblasts by miR-200b represses chemoresistance and epithelial-mesenchymal transition of gastric cancer cells.

Background: Cancer-associated fibroblasts (CAFs) are vital components of gastric cancer (GC) microenvironments, which impact the aggressive characteristics of GC cells. The objective of this study is to evaluate the influence of High Mobility Group Box (HMGB) on CAF-related GC. Methods: The tissues of 10 GC patients who underwent surgery the Sanya Central Hospital of Hainan Province from July 2018 to July 2019 were collected for the clinical study. Moreover, the GC cell lines, including MGC-803, AGS, and SGC-7901, were used in vitro experiment. We investigated the molecular mechanism of the miR-200b/HMGB3 axis in affecting the chemoresistance and epithelial-mesenchymal transition (EMT) of GC cells induced by CAFs. Cell transfection, Cell Counting Kit-8 (CCK-8), Transwell assay, western blot, enzyme-linked immunosorbent assay (ELISA), and other experiments were employed. Results: We found that miR-200b was down-regulated, yet HMGB3 was up-regulated in CAF-related GC. The CAFs markedly promoted cisplatin (CDDP) resistance, proliferation, invasion, migration, and EMT of GC cells. Gain-assay of miR-200b demonstrated that miR-200b inhibited the HMGB3 release from CAFs. In-vivo experiments confirmed that the growth and EMT of GC cells co-cultured with CAF-miR-200b were significantly reduced. Furthermore, CAFs enhanced the activation of ERK, JNK, and the Wnt/ß-catenin pathways, and those pathways, as well as the malignant behaviors of GC cells, were obviously attenuated by miR-200b or HMGB3 silencing. Conclusions: Collectively, HMGB3 derived from CAFs is negatively regulated by miR-200b and promotes the malignant behaviors of GC cells.

PCDH7 knockdown potentiates colon cancer cells to chemotherapy via inducing ferroptosis and changes in autophagy through restraining MEK1/2/ERK/c-Fos axis.

Chemotherapy is a commonly utilized treatment strategy for colon cancer, a prevalent malignancy. The study intends to probe the function and mechanism of protocadherin 7 (PCDH7) in colon cancer. Gain or loss of functional assays of PCDH7 was performed. MTT and colony formation assay monitored cell proliferation. Transwell measured migration and invasion. Real-time quantitative polymerase chain reaction and western blot verified the profiles of PCDH7 and the MEK1/2/ERK/c-FOS pathway. Western blot was implemented to confirm the profiles of PP1α, MLC2, and p-MLC2 for evaluating the impact of PCDH7 on homotypic cells in cell (hocic) structures. Further, an in-vivo nude mouse model was engineered to figure out the function and mechanism of PCDH7 in tumor cell growth. As indicated by the data, PCDH7 knockdown boosted the cells' sensitivity to chemotherapy. PCDH7 overexpression facilitated their proliferation and invasion, altered autophagy, induced ferroptosis and hocic, and initiated the profile of the MEK1/2/ERK/c-FOS pathway. MEK1/2/ERK inhibition impaired the inhibitory impact of PCDH7 on colon cancer cells' chemotherapy sensitivity and dampened its pro-cancer function in the cells. In-vivo experiments displayed that PCDH7 overexpression stepped up tumor growth and pulmonary metastasis in colon cancer cells. All in all, the research has discovered that PCDH7 knockdown affects autophagy and induces ferroptosis, hence strengthening colon cancer cells' sensitivity to chemotherapy by repressing the MEK1/2/ERK/c-FOS axis.

Identification of GPX4 as a therapeutic target for lung adenocarcinoma after EGFR-TKI resistance.

Background: Tyrosine kinase inhibitor (TKI) treatment has significantly improved the prognosis of oncogenic-driven lung adenocarcinoma (LUAD). However, drug resistance limits the long-term benefits of patients. Therefore, there is a pressing need to explore the mechanism of TKI resistance and identify new therapeutic targets. It is possible to overcome TKI resistance by inducing tumor cell death through a new process called ferroptosis. Aberrations in ferroptosis, which is a kind of regulated cell death (RCD), has been confirmed to be involved in the development and progression of multiple tumors, and is closely related to patient survival. At present, the role of ferroptosis in TKI resistance remains unclear. Methods: Ferroptosis-related factors were isolated by expression characteristics analysis based on the multi-omics data of LUADs and normal lung tissues from The Cancer Genome Atlas (TCGA) database. Next, expression of selected ferroptosis-related factors and prognosis were analyzed. Subsequently, the differences in the expression of selected ferroptosis-related factors before and after TKI resistance on a variety of LUAD cell lines were analyzed to identify the factors that were involved in TKI resistance. Finally, the therapeutic effects were confirmed in vitro by targeting the selected ferroptosis-related factors with small molecule compounds. Results: Glutathione Peroxidase 4 (GPX4), a ferroptosis-related factor, was up-regulated in tumor tissue of LUADs, and correlated with the prognosis of patients. By detecting the expression change of GPX4 before and after TKI resistance in a variety of LUAD cell lines, we confirmed that the inhibition of GPX4 could overcome epidermal growth factor receptor (EGFR)-TKI resistance by inducing ferroptosis. Conclusions: GPX4 could serve as a novel therapeutic target for EGFR-TKI resistance in LUAD.

Synchronous resection of 12 small pulmonary nodules guided by a noninvasive 3D printed emulation model: A case report.

Localization of multiple small pulmonary nodules is the major obstacle in surgical resection. Here, we report a novel noninvasive localization technique based on a life-size 3D printed "emulation pulmonary nodule localization model" which is simple and efficient. In the case reported here of a patient with synchronous multiple pulmonary nodules, the nodules were successfully and conveniently localized without any trauma by navigation of the emulation localization model. All 12 nodules were resected precisely and thoroughly, while normal lung tissues were considerably well preserved. Pathological examination confirmed malignancy of the major nodule and some other small nodules.

Identifies Immune Feature Genes for Prediction of Chemotherapy Benefit in Cancer.

Chemotherapy is still the most fundamental treatment for advanced cancers so far. Previous studies have indicated that immune cell infiltration (ICI) index could serve as a biomarker to predict chemotherapy benefit in breast cancer and colorectal cancer. However, due to different responses of tumor infiltrating immune cells (TIICs) to chemotherapy, the prediction efficiency of ICI index is not fully confirmed by now. In our study, we first extended this conclusion in 7 cancers that high ICI index could certainly indicate chemotherapy benefit (P<0.05). But we also found the fraction of different TIICs and the interaction of TIICs were varies greatly from cancer to cancer. Therefore, we executed correlation and causal network analysis to identify chemotherapy associated immune feature genes, and fortunately identified six co-owned immune feature genes (CD48, GPR65, C3AR1, CD2, CD3E and ARHGAP9) in 10 cancers (BLCA, BRCA, COAD, LUAD, LUSC, OV, PAAD, SKCM, STAD and UCEC). Base on this, we developed a chemotherapy benefit prediction model within six co-owned immune feature genes through random forest classifying (AUC =0.83) in cancers mentioned above, and validated its efficiency in external datasets. In short, our work offers a novel model with a shrinking panel which has the potential to guide optimal chemotherapy in cancer.

Perioperative ctDNA-Based Molecular Residual Disease Detection for Non-Small Cell Lung Cancer: A Prospective Multicenter Cohort Study (LUNGCA-1).

PURPOSE: We assessed whether perioperative circulating tumor DNA (ctDNA) could be a biomarker for early detection of molecular residual disease (MRD) and prediction of postoperative relapse in resected non-small cell lung cancer (NSCLC). EXPERIMENTAL DESIGN: Based on our prospective, multicenter cohort on dynamic monitoring of ctDNA in lung cancer surgery patients (LUNGCA), we enrolled 950 plasma samples obtained at three perioperative time points (before surgery, 3 days and 1 month after surgery) of 330 stage I-III NSCLC patients (LUNGCA-1), as a part of the LUNGCA cohort. Using a customized 769-gene panel, somatic mutations in tumor tissues and plasma samples were identified with next-generation sequencing and utilized for ctDNA-based MRD analysis. RESULTS: Preoperative ctDNA positivity was associated with lower recurrence-free survival (RFS; HR = 4.2; P < 0.001). The presence of MRD (ctDNA positivity at postoperative 3 days and/or 1 month) was a strong predictor for disease relapse (HR = 11.1; P < 0.001). ctDNA-based MRD had a higher relative contribution to RFS prediction than all clinicopathologic variables such as the TNM stage. Furthermore, MRD-positive patients who received adjuvant therapies had improved RFS over those not receiving adjuvant therapy (HR = 0.3; P = 0.008), whereas MRD-negative patients receiving adjuvant therapies had lower RFS than their counterparts without adjuvant therapy (HR = 3.1; P < 0.001). After adjusting for clinicopathologic variables, whether receiving adjuvant therapies remained an independent factor for RFS in the MRD-positive population (P = 0.002) but not in the MRD-negative population (P = 0.283). CONCLUSIONS: Perioperative ctDNA analysis is effective in early detection of MRD and relapse risk stratification of NSCLC, and hence could benefit NSCLC patient management.

Sentinel lymph node biopsy in head and neck cutaneous melanomas: A PRISMA-compliant systematic review and meta-analysis.

BACKGROUND: Head and neck melanomas (HNMs) behave differently from cutaneous melanomas in other sites, and the efficacy of sentinel lymph node biopsy (SLNB) for patients with HNMs remains controversial. METHODS: Studies on prognosis following SLNB were included. The prognostic role of SLNB and other potential predictors were analyzed using pooled relative risk (RR) or hazard ratio (HR). RESULTS: Pooled statistics showed that SLNB improved overall survival of HNMs patients (HR = 0.845; 95% CI: 0.725-0.986; P = .032). The positive status of SN was proved as a risk factor of poor prognosis in HNMs (HR = 3.416; 95% CI: 1.939-6.021; P < .001). SLNB did not have significant correlation with lower recurrences (RR = .794; 95% CI: 0.607-1.038; P = .091). CONCLUSIONS: SLNB is associated with better overall survival and the SN status is a promising risk factor of poor prognosis for HNMs patients.

A comprehensive comparison of residue-level methylation levels with the regression-based gene-level methylation estimations by ReGear.

MOTIVATION: DNA methylation is a biological process impacting the gene functions without changing the underlying DNA sequence. The DNA methylation machinery usually attaches methyl groups to some specific cytosine residues, which modify the chromatin architectures. Such modifications in the promoter regions will inactivate some tumor-suppressor genes. DNA methylation within the coding region may significantly reduce the transcription elongation efficiency. The gene function may be tuned through some cytosines are methylated. METHODS: This study hypothesizes that the overall methylation level across a gene may have a better association with the sample labels like diseases than the methylations of individual cytosines. The gene methylation level is formulated as a regression model using the methylation levels of all the cytosines within this gene. A comprehensive evaluation of various feature selection algorithms and classification algorithms is carried out between the gene-level and residue-level methylation levels. RESULTS: A comprehensive evaluation was conducted to compare the gene and cytosine methylation levels for their associations with the sample labels and classification performances. The unsupervised clustering was also improved using the gene methylation levels. Some genes demonstrated statistically significant associations with the class label, even when no residue-level methylation features have statistically significant associations with the class label. So in summary, the trained gene methylation levels improved various methylome-based machine learning models. Both methodology development of regression algorithms and experimental validation of the gene-level methylation biomarkers are worth of further investigations in the future studies. The source code, example data files and manual are available at http://www.healthinformaticslab.org/supp/.

Discovery of lung surface intersegmental landmarks by three-dimensional reconstruction and morphological measurement.

BACKGROUND: The lack of anatomic landmarks between segments on the lung surface makes the identification of intersegmental planes one of the greatest challenges in anatomic segmentectomy. Therefore, with the aim to determine the landmarks of intersegmental planes on the lung surface, we used three-dimensional (3D) reconstruction and morphological measurement techniques to reconstruct stereoscopic models of all pulmonary segments, and measured the length of each segment on the lung surface along the lobe's anatomic landmark lines. METHODS: We downloaded the primary computed tomography (CT) scan data of 619 patients and imported them into a 3D reconstruction system, which could automatically reconstruct the 3D model of the trachea-bronchi system. We manually reconstructed the intersegmental veins to ensure the accuracy of segmental boundary. The 3D models of pulmonary segments could be reconstructed based on the bronchial tree and the pathways of the intersegmental veins. We then measured the length of each segment on the lung surface along the lobe's anatomic landmark lines and calculated the proportions between these lengths. RESULTS: Complete 3D segmental models were successfully reconstructed in 500 patients (241 male and 259 female), and the lengths of every segment on the lung surface along the lobe's anatomic landmark lines were measured. Our data revealed that the length of each segment on lung surface varied among individuals. However, the proportions between these lengths stayed constant, even when stratified by gender, age, height, and weight. CONCLUSIONS: We discovered that the proportion between the lengths of adjacent segments on the lung surface stayed constant. The constant proportion reflected and uncovered the lung surface intersegmental landmarks, which could help direct surgeons to identify intersegmental planes during anatomic segmentectomy in an easy and safe way without additional cost.

Three-dimensional versus two-dimensional video-assisted thoracic surgery for thoracic disease: a meta-analysis.

OBJECTIVES: It remains unclear whether 3D systems are manoeuvrable in video-assisted thoracic surgery (VATS) for patients with thoracic diseases. The objective of this systematic review and meta-analysis was to evaluate the efficacy and safety of 3D VATS compared with 2D VATS. METHODS: A systemic research of the literature was performed using the PubMed, Embase, the Cochrane library, China National Knowledge Infrastructure, Wanfang and CQVIP databases through December 2016. Studies investigating the efficacy and safety of 3D VATS compared with 2D VATS were eligible for our meta-analysis. Odds ratios and mean differences or standard mean differences with 95% confidence intervals (95% CI) as well as a P-value were applied to compare continuous and dichotomous variables, respectively. RESULTS: Seven studies with 1080 patients (525 patients for 3D VATS and 555 patients for 2D VATS) were included. There were significant differences in the 3D group with regard to shorter operation times (standard mean difference = -0.66, 95% CI: -0.98 to - 0.34; P < 0.001), less blood loss (mean difference = -12.12, 95% CI: -19.07 to - 5.16; P < 0.001) and shorter postoperative drainage times (standard mean difference = -0.53, 95% CI: -0.92 to - 0.14; P = 0.008) compared with the 2D group. However, no statistical difference was found for postoperative hospital stay, total postoperative drainage volume, postoperative drainage volume in 24 h, number of lymph nodes dissected and postoperative complications. CONCLUSIONS: The results of this systematic review and meta-analysis suggest that 3D VATS might be an acceptable method for treating thoracic diseases in the future.

The role of serum angiopoietin-2 levels in progression and prognosis of lung cancer: A meta-analysis.

BACKGROUND: Angiogenesis is an essential process in the development and progression of malignant tumors including lung cancer, in which angiopoietin-2 (Ang-2) plays an important role. The objective of this study was to assess the prognostic value of serum Ang-2 levels in patients with lung cancer. METHODS: A comprehensive systematic electronic search was performed in the Pubmed, Embase, Web of Science, china national knowledge infrastructure, and VIP databases update to October, 2016 (qikan.cqvip.com). Literatures examining the relevance of serum Ang-2 levels to progression and prognosis of lung cancer were eligible for our study. Standardized mean differences (SMD) with 95% confidence interval (95% CI) and a P value were applied to compare continuous variables, and hazard ratio (HR) with 95% CI as well as P value were applied for prognostic role. RESULTS: Twenty studies with 1911 patients met the eligibility criteria. Among them, 7 studies with 575 patients with lung cancer assessed the association between expression of serum Ang-2 and prognosis. According to our results, higher levels of serum Ang-2 were associated with the later stage of tumor. Serum Ang-2 levels were significantly lower in stage I than in stage II (SMD: -0.51; 95% CI: -0.75 to -0.27; P < .001), in stage II than in stage III (SMD: -0.52; 95% CI: -0.80 to -0.24; P < .001), in stage III than in stage IV (SMD: -0.58; 95% CI: -0.93 to -0.23; P = .001). In addition, serum Ang-2 levels were higher in patients with lymph node metastasis (SMD: 1.06; 95% CI, 0.57-1.56; P < .001). Meanwhile, patients with lung cancer with higher levels of serum Ang-2 were associated with a significant poorer prognosis when compared to those with lower serum Ang-2 levels (HR: 1.64; 95% CI: 1.20-2.25; P = .002), and this role was further detected when stratified by ethnicity and histological type. CONCLUSIONS: This systematic review and meta-analysis suggested that serum Ang-2 levels might be a potential predictor for staging, and were associated with prognosis of lung cancer.

Should primary tumor be resected for non-small cell lung cancer with malignant pleural disease unexpectedly found during operation?-a systemic review and meta-analysis.

BACKGROUND: Non-small cell lung cancer (NSCLC) with malignant pleural disease (MPD) was considered to be contraindication for surgery, but sometimes MPD was unexpectedly found intraoperatively. There was no consensus on the role of surgical intervention on the primary tumor in patients with MPD. The object of this research was to assess whether exairesis of primary tumor could prolong survival time. METHODS: A systemic research of literature was performed on the databases of PubMed, Embase and Web of Science. Literatures examining surgical benefit or other prognostic factors among NSCLC patients with MPD unexpectedly found during operations were included. Hazard ratio (HR) with 95% confidence interval (95% CI) as well as P value is applied for prognostic role of surgical removal or other potential factors. RESULTS: Nine articles with a total number of 861 patients fulfilled the eligibility criteria, five of them compared the survival benefit between exploration and resection among NSCLC patients with unexpected MPD, and other studies also investigated the prognostic factors in these patients. There was a significant survival benefit in patients with primary tumor resection (HR =0.443; 95% CI: 0.344-0.571; P<0.001). This role was further detected when stratified by analysis method and ethnicity. Female was an independent favorable predicted factor (HR =0.788; 95% CI: 0.648-0.959; P=0.017) while higher N-stage was a risk factor (HR =1.879; 95% CI: 1.307-2.701; P=0.001). Among patients who received primary tumor resection, higher N-stage was also a risk factor for poorer survival (HR =2.021; 95% CI: 1.496-2.730; P<0.001). CONCLUSIONS: Resection of primary tumor, female and lower-N stage were suggested to be beneficial prognostic factor among NSCLC patients who were detected with MPD for the first time in the operating room. And among these people who received surgical removal of primary tumor, lower N-stage also indicated a better survival.